Human blood serum contains lipoproteins whose values are traditionally determined by a lipid panel and used by physicians to diagnosis and treat patients for cardiovascular disease.
The National Cholesterol Education Program (NCEP) acknowledges that 50% of the people with cardiovascular disease are missed by the standard lipid panel tests for total cholesterol, triglycerides, high density lipoprotein (HDL) and calculated low density lipoprotein (LDL). NCEP described in the latest ATP III (Adult Treatment Program III) guidelines, new emerging risk factors that are important in the diagnosis and treatment of those people missed by the standard lipid panel. NCEP does not generally recommend analysis of the new emerging risk factors due to the lack of availability and the cost of these tests. None the less a number of companies have emerged to address this need and supply information on these risk factors.
Lipoproteins are spherical particles composed of hundreds to thousands of molecules. Each particle has at least one apolipoprotein which distinguishes it as a VLDL, LDL, or HDL particle. VLDL and LDL particles have one molecule of apolipoprotein B and HDL molecules have one or more molecules of apolipoprotein A on the surface of the particle. In addition, the surface of the particle is covered with phospholipids and unesterified cholesterol. The interior of lipoproteins is composed of cholesterol ester and triglycerides with most of the triglycerides being found in the VLDL lipoprotein.
In the Standard Lipid Panel, LDL is calculated (not directly measured) from assumptions about the cholesterol content of very low density lipoprotein (VLDL) knowing the triglyceride values and directly measured total cholesterol and HDL. This result can have a 20% or larger LDL cholesterol error as determined in studies and even greater error when compared to lipoprotein particle numbers. LDL measured directly for cholesterol content is a somewhat better measurement. However, high or very low triglycerides and other substances can interfere, precluding accurate results. The cholesterol, as a surrogate marker, is assumed to correlate with LDL particle numbers. This is not the case for many individuals, giving up to a 30% or greater error when compared to particle number values.
A number of methods have been developed as cost and time saving alternatives to the CDC method of cholesterol analysis to provide information on the new lipoprotein emerging risk factors as identified in the NCEP guidelines for the diagnosis and treatment of people at risk of cardiovascular disease. Historically, the CDC method using gradient separation of the lipoproteins in the blood by analytical ultracentrifugation is know as the gold standard in identifying the lipoprotein classes of VLDL, LDL and HDL. The CDC method, however does not break down lipoproteins into subgroups which are necessary for the identification of the new emerging risk factors. To extend the CDC method with sequential multiple gradient separations of subgroups is very time consuming and expensive. In view of these problems other methods have been developed to give information that approximates an extended CDC sequential separation with techniques that are faster and/or less costly than the CDC method.
Thus, there is considerable room for improvement in the development of a new test which more accurately indicates risk of cardiovascular disease (CVD).